Copper-promoted site-selective carbonylation of sp³ and sp² C-H bonds with nitromethane

Copper-promoted direct carbonylation of unactivated sp³ C-H and aromatic sp² C-H bonds of amides was developed using nitromethane as a novel carbonyl source. The sp³ C-H functionalization showed high site-selectivity by favoring the C-H bonds of α-methyl groups. The sp² C-H carbonylation featured high regioselectivity and good functional group compatibility. Kinetic isotope effect studies indicated that the sp³ C-H bond breaking step is reversible, whereas the sp² C-H bond cleavage is an irreversible but not the rate-determining step. Control experiments showed that a nitromethyl intermediate should be involved in the present reaction.